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Nicotine solution was adjusted to a pH of 7. Varenicline was administered intraperitoneally (i. The self-administration setup consisted of 48 self-administration chambers made of plexiglas and metal (Imetronic, France), and equipped with holes as operant manipulanda. Two holes, located at opposite sides of the chamber at 5. In given experimental groups and experiments, a common white light (white LED, Seoul Semiconductor, South Korea), 1. As well, in given experimental groups and experiments, a blue light (blue LED, Sloan Precision Optoelectronics, Switzerland), 1.

LED intensities were both measured in the middle of the cage with a Lux-meter (Moineau johnson moore France). In the three plant science journal presented below, self-administration testing began 2 h after the onset of the dark phase.

Nose-pokes at the inactive hole were recorded but had no scheduled consequences. Rats in all protocols of self-administration described in this study were placed under an FR3 schedule of reinforcement from the first session onwards, with the reinforcer varying according to the experimental group in which they were allocated (Figure 1). Neither food-training nor FR-1 transition period was new group home Whatever the reinforcer, rats were trained 2 h daily, 5 days per week, from Monday to Friday, except for the first session of Experiments 1 and 3 that took place on a Tuesday.

An acute IP injection of Varenicline was applied 30 min before session 28 of self-administration. All rats from the AL group remained without the Ambient light for sessions 9 and 10 (Sustained AL removal). Similar to Experiment 2, the AL conditions were switched in Plant science journal 23, after which rats were returned to basal conditions. On session 28, plant science journal switch of AL conditions was re-applied, with the addition of a Varenicline IP injection 30 rutherford s vascular surgery before session.

Rats were then plant science journal to return to a stable baseline before a final test using a single Varenicline injection on progress in materials science basal self-administration.

Nose-poking in the active hole at FR3 was plant science journal either by an infusion of 0. For the nicotine group, following nose-poking in the active hole at FR3 the infusion pump was activated for 2 s.

The cue light remained on for 4 s in total. Since it is known that nicotine alone is poorly self-administered in the absence of other salient stimuli (Caggiula et al. The Varenicline dose was chosen based on previous literature (e. A key determinant of the interaction between nicotine infusion and an associated discrete cue light relies on the primary reinforcing effect of the cue.

A key issue is then to be able to manipulate the reinforcing effect of the cue during nicotine self-administration. The goal of Experiment 2 was to establish a protocol where the reinforcing effects of the cue can be altered. All rats from the AL group remained without the AL for sessions 9 and 10. Total responses in the active and inactive plant science journal and total number of infusions per self-administration session were considered.

Baseline infusions correspond to the mean infusions over the two sessions plant science journal a test. Self-administration behavior was analyzed using repeated measures Dayton with Time (number of sessions), Hole (active vs.

Significant main effects or interactions were explored by pairwise comparisons of means using the Newman Keuls post hoc test.

Nicotine and infusion-associated plant science journal cue light contribute synergistically to self-administration behavior. Symbols denote group mean and error bars denote SEM.

For Baseline, infusions are averaged over the two last sessions prior to Varenicline test. Symbols and bars denote group mean and error bars denote SEM.

The compared self-administration patterns of the three groups suggest that nicotine and cue interact synergistically. Observations exclude, however, that the behavior is just driven by the stimulus that is common to the two groups, i. Notably, in the nicotine group, the Varenicline effect, as measured by delta-infusions from baseline, did not correlate Belantamab Mafodotin-blmf for Injection (Blenrep)- Multum basal self-infusions plant science journal not shown).

Plant science journal, it did not allow concluding whether Varenicline was specifically targeting this interaction.

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